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Background: There are limited data on the physical effects of androgen deprivation therapy (ADT) for prostate cancer (PC), and on the relationships of such measures of adiposity and strength to cardiovascular outcomes., Objectives: The primary objective of this study was to evaluate the relationships of measures of adiposity and strength to cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, heart failure, arterial revascularization, peripheral arterial disease, and venous thromboembolism) in patients with PC. A secondary objective was to characterize the relationships between ADT use and 12-month changes in these physical measures., Methods: This international, prospective cohort study included 3,967 patients with PC diagnosed in the prior 12 months or being treated with ADT for the first time. Median follow-up duration was 2.3 years., Results: Participants' mean age was 68.5 years, and 1,731 (43.6%) were exposed to ADT. ADT was associated with a 1.6% increase in weight, a 2.2% increase in waist circumference, a 1.6% increase in hip circumference, a 0.1% increase in waist-to-hip ratio, a 27.4% reduction in handgrip strength, and a 0.1% decrease in gait speed. High waist circumference and low handgrip strength were associated with adverse cardiovascular outcomes. Adjusting for age, education, race, tobacco and alcohol use, physical activity, cardiovascular disease, glomerular filtration rate, and ADT use, waist circumference above the highest quartile (110 cm) and handgrip strength below the lowest quartile (29.5 kg) were associated with higher likelihoods of a future cardiovascular event, with respective HRs of 1.40 (95% CI: 1.03-1.90; P  = 0.029) and 1.59 (95% CI: 1.14-2.22; P  = 0.006)., Conclusions: ADT was associated with increased adiposity and reduced strength over 12-month follow-up. High waist circumference and low baseline strength were associated with future adverse cardiovascular outcomes., Competing Interests: Research support for this study was provided by the Movember Foundation, the Canadian Cancer Society, and Tolmar Pharmaceuticals. This study was presented in part at a Late-Breaking Science Session at the Scientific Sessions of the European Society of Cardiology, Amsterdam, the Netherlands, August 28, 2023. Dr Leong has received consultancy fees or honoraria from Abbvie, Ferring, Ipsen, Janssen, Jazz Pharmaceuticals, Myovant, Novartis, Pfizer, Sanofi, Antev, AstraZeneca, Bayer, Boston Scientific, and XFacto; and has received research support from Novartis and Tolmar. Dr Higano has received consultancy fees or honoraria from AstraZeneca, Astellas, Bayer, Genetech, Eli Lilly, Merck Sharp & Dohme, Myovant, Menarini, Tolmar, Vaccitech, and Verity; is a stockholder of CTI Biopharma; and is a data and safety monitoring board member or chair in trials sponsored by AstraZeneca, Advantagene, and Exelixis. Dr Lavallée is an advisory board member for Astellas, Knight, Bayer, and AAA; and has received a grant from Tolmar unrelated to the present work. Dr Gopaul is an advisory board member for and has received honoraria from TerSera, Bayer, Ferring, Abbvie, and Knight. Dr Duceppe has received grant funding from Roche Diagnostics and Abbott Laboratories. Dr Guha is an advisory board member for Pfizer, Myovant, and Novartis; and has received research grants from the American Heart Association (847740 and 863620) and the U.S. Department of Defense PC Research Program (HT94252310158). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers., Methods: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint)., Results: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity ( p = 0.51) between the DPP-4i (8.00 {-65.00; 63.00}) and placebo (-14.00 {-77.00; 52.00}) groups, as well in mean BNP levels ( p = 0.14) between DPP-4i (-36.00 {-110.00; 15.00}) and placebo (-13.00 {-50.00; 27.00}). There was no difference between groups in cardiac adverse events., Conclusions: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Background: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications., Objectives: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding., Methods: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y 12 receptor inhibitors, were assigned to either control group, P2Y 12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units)., Results: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003)., Conclusions: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267)., Competing Interests: Funding Support and Author Disclosures This study was financed in part by the Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES) – Finance Code 001. Dr. Furtado has received grants and personal fees from AstraZeneca; personal fees from Servier; and grants from EMS, Pfizer, Novo Nordisk, DalCor, Novartis, and Janssen, all outside the submitted work. Dr. Baracioli has received personal fees from Sandoz. Dr. Barbosa has received personal fees from Bayer, Daiichi-Sankyo, and Servier. Dr. Britto has received research grants from Novo Nordisk, DalCor, AstraZeneca, and Novartis. Dr. Farkouh has received research grants from Amgen, Novartis, and Novo Nordisk. Dr. Gurbel has received consultant and/or receives honoraria from Bayer, Merck, Janssen, Medicure, and USWorld Meds; has received grants from the National Institutes of Health, Janssen, Merck, Bayer, Haemonetics, Instrumentation Labs, and Amgen; holds stock or stock options in Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Nicolau has received personal fees from AMGEN; has received grants from AstraZeneca, Bristol Myers Squibb, CLS Behring, Dalcor, Janssen, NovoNordisk, and Vifor; has received grants and personal fees from Bayer, Novartis, and Sanofi; and has received personal fees from Daiichi-Sankyo and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS)., Objective: To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS., Methods: This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant., Results: A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization., Conclusions: Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294).

Objectives: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS., Methods: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed., Results: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables., Conclusions: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.

Introduction: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability., Methods: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints)., Results: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran., Conclusions: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran., Trial Registration: ClinicalTrials.gov identifier, NCT02389582.

Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100 mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value = 0.012) increase in ARU for every 10 kg. Furthermore, the rate of non-response to aspirin (defined as ARU ≥ 550) was significantly associated with increased bodyweight (adjusted p-value = 0.007), with OR = 1.23 (95% CI 1.06-1.42) for every 10 kg. Similar results were found considering body mass index (in kg/m 2 ), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value = 0.004) increase in ARU for every 10 kg and non-response OR = 1.43 (95% CI 1.13 to 1.81, adjusted p-value = 0.003) for every 5 kg/m 2 . Moreover, serum TXB2 was higher in patients weighting more than 70 kg (222.6 ± 62.9 versus 194.9 ± 61.9 pg/mL; adjusted p-value = 0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100 mg QD, increased bodyweight was independently associated with impaired response to aspirin.